Genetic Variant NM_001001995.3:c.182-33G>A (chrX-13785841-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001001995.3(GPM6B):c.182-33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 13958 hom., 19562 hem., cov: 23)

Exomes 𝑓: 0.60 ( 123171 hom. 191233 hem. )

Failed GnomAD Quality Control

Consequence

GPM6B
NM_001001995.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.783

Publications

5 publications found

Variant links:

Genes affected

GPM6B (HGNC:4461): (glycoprotein M6B) This gene encodes a membrane glycoprotein that belongs to the proteolipid protein family. Proteolipid protein family members are expressed in most brain regions and are thought to be involved in cellular housekeeping functions such as membrane trafficking and cell-to-cell communication. This protein may also be involved in osteoblast differentiation. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are located on chromosomes Y and 22. [provided by RefSeq, Jan 2016]

GPM6B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPM6B	NM_001001995.3 link	c.182-33G>A		intron_variant	Intron 2 of 7	ENST00000316715.9	NP_001001995.1	Q13491-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPM6B	ENST00000316715.9 link	c.182-33G>A		intron_variant	Intron 2 of 7	2	NM_001001995.3	ENSP00000316861.4		Q13491-4

Frequencies

GnomAD3 genomes

AF:

0.599

AC:

66027

AN:

110261

Hom.:

13961

Cov.:

show subpopulations

Gnomad AFR

AF:

0.618

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.549

Gnomad SAS

AF:

0.631

Gnomad FIN

AF:

0.600

Gnomad MID

AF:

0.526

Gnomad NFE

AF:

0.578

Gnomad OTH

AF:

0.598

GnomAD2 exomes

AF:

0.625

AC:

95747

AN:

153076

AF XY:

0.632

show subpopulations

Gnomad AFR exome

AF:

0.620

Gnomad AMR exome

AF:

0.794

Gnomad ASJ exome

AF:

0.563

Gnomad EAS exome

AF:

0.559

Gnomad FIN exome

AF:

0.608

Gnomad NFE exome

AF:

0.583

Gnomad OTH exome

AF:

0.618

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.598

AC:

611623

AN:

1022670

Hom.:

123171

Cov.:

AF XY:

0.634

AC XY:

191233

AN XY:

301412

show subpopulations

African (AFR)

AF:

0.620

AC:

15416

AN:

24851

American (AMR)

AF:

0.783

AC:

25802

AN:

32948

Ashkenazi Jewish (ASJ)

AF:

0.572

AC:

10299

AN:

17999

East Asian (EAS)

AF:

0.552

AC:

16268

AN:

29483

South Asian (SAS)

AF:

0.646

AC:

32124

AN:

49733

European-Finnish (FIN)

AF:

0.605

AC:

23942

AN:

39594

Middle Eastern (MID)

AF:

0.510

AC:

1943

AN:

3813

European-Non Finnish (NFE)

AF:

0.589

AC:

460207

AN:

780940

Other (OTH)

AF:

0.592

AC:

25622

AN:

43309

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

8659

17318

25977

34636

43295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14578

29156

43734

58312

72890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.599

AC:

66065

AN:

110316

Hom.:

13958

Cov.:

AF XY:

0.600

AC XY:

19562

AN XY:

32590

show subpopulations

African (AFR)

AF:

0.618

AC:

18711

AN:

30280

American (AMR)

AF:

0.674

AC:

7020

AN:

10420

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

1477

AN:

2631

East Asian (EAS)

AF:

0.550

AC:

1913

AN:

3480

South Asian (SAS)

AF:

0.633

AC:

1632

AN:

2578

European-Finnish (FIN)

AF:

0.600

AC:

3493

AN:

5822

Middle Eastern (MID)

AF:

0.514

AC:

109

AN:

212

European-Non Finnish (NFE)

AF:

0.578

AC:

30459

AN:

52717

Other (OTH)

AF:

0.601

AC:

907

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

976

1952

2927

3903

4879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.517

Hom.:

6672

Bravo

AF:

0.608

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0040

(source)

DANN

Benign

0.43

PhyloP100

-0.78

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over